1. Field of the Invention
The present invention relates to a method of preparing 3-benzyl-6-cyanomethyl-2,5-dioxopiperazine, which is an intermediate in the preparation of an .alpha.-L-aspartyl-L-phenylalanine methyl ester derivative and to a method of preparing an .alpha.-L-aspartyl-L-phenylalanine methyl ester (.alpha.-APM) derivative.
2. Discussion of the Background
.alpha.-L-aspartyl-L-phenylalanine methyl ester (Aspartame, .alpha.-APM) is in heavy demand as a good low-calorie sweetener. The .alpha.-APM derivative as referred to herein is a generic name for a group of compounds which include .alpha.-APM, .alpha.-L-aspartyl-L-phenylalanine dimethyl ester, .alpha.-L-aspartyl-L-phenylalanine-.beta.-methyl ester and .alpha.-L-aspartyl-L-phenylalanine, each of which can be converted to .alpha.-APM with relative ease by conventional methods (see Japanese Patent Application Laid-open Nos. 59-219258 and 59-225152 and U.S. Pat. No. 4,173,562). A variety of methods have previously been proposed for preparing .alpha.-APM, which are based on chemically or enzymatically condensing L-aspartic acid or a derivative thereof and L-phenylalanine or a derivative thereof (see Kirk-Othmer's Encyclopedia of Chemical Technology, vol. 22, pp 453-458 (1983); R. H. Mazur et al, J. Med. Chem., 91, 2684 (1969); Y. Ariyoshi et al. Bull Chem. Soc. SpA. 46, 1893 (1973); Y. Ariyoshi Kagakuto Seibutsu 12, 189 (1974); Chem. Abstr. 82, 1120u (1975); F. J. Vinick, U.S. Pat. No. 4,256,897; F. J. Vinick et al, Tetrahedron Lett 23, 1315 (1982); W.H.J. Boesten, U.S. Pat. No. 3,879,372; G. L. Bachman, U.S. Pat. No. 3,933,781, A. Yasutake et al, Bull. Chem. Soc. Jpn. 50, 2413 (1977); Isowa et al., Tetrahedron Lett. 20, 7611 (1979)). However, no method of preparing .alpha.-APM has been proposed which does not involve the use of L-phenylalanine or a derivative thereof. Such a method would be desirable in order to reduce the production cost of .alpha.-APM by eliminating the need to use the expensive L-phenylalanine as raw materials.